Integrin-mediated mechanotransduction processes in TGFβ-stimulated monolayer-expanded chondrocytes

Previous studies have demonstrated that passage in monolayer detrimentally affects the response of articular chondrocytes to the application of dynamic compression. Transforming growth factor β (TGFβ) is known to regulate metabolic processes in articular cartilage and can enhance the re-expression of a chondrocytic phenotype following monolayer expansion. The current study tests the hypothesis that TGFβ also modulates the response of monolayer-expanded human chondrocytes to the application of dynamic compression, via an integrin-mediated mechanotransduction process. The data presented demonstrate that TGFβ 3 enhanced 35 SO 4 and [ 3 H]thymidine incorporation and inhibited nitrite release after 48 h of culture when compared to unsupplemented constructs. Dynamic compression also enhanced 35 SO 4 and [ 3 H]thymidine incorporation and inhibited nitrite release in the presence of TGFβ 3 . By contrast, dynamic compression did not alter these parameters in the absence of the growth factor. The addition of the peptide, GRGDSP, which acts as a competitive ligand for the α5β1 integrin, reversed the compression-induced stimulation of 35 SO 4 incorporation, [ 3 H]thymidine incorporation, and suppression of nitrite release. No effect was observed when the control peptide, GRADSP, was used. The current data clearly demonstrate that the dynamic compression-induced changes observed in cell metabolism for human monolayer-expanded chondrocytes were dependent on the presence of TGFβ 3 and are integrin-mediated.